In a highly complex modern society, a reduction of willingness turns into a problem. For example, the term “motivation crisis” is used to describe the problem of reduced motivation in young people. Moreover, it is said that depression patients often show symptoms of hypobulia, and there is a demand for the development of drugs capable of improving hypobulia.
Therapeutic or prophylactic agents for depression currently used in clinical cases are tricyclic antidepressants and tetracyclic antidepressants, as well as selective serotonin reuptake inhibitors (hereinafter referred to as “SSRI”) and serotonin/noradrenaline reuptake inhibitors (hereinafter referred to as “SNRI”). SSRI and SNRI are antidepressants that are designed to greatly reduce the side effects of conventional tricyclic antidepressants (Journal of clinical and experimental medicine (Igaku no Ayumi), Vol. 219, No. 13, 963-968, 2006). However, although these side effects have been reduced, SSRI and SNRI are reported still to have other side effects.
In terms of safety, there are reports of various therapeutic or prophylactic agents for depression, which comprise a component(s) extracted from naturally occurring products as their active ingredient. For example, a ginkgo leaf extract which is a component extracted from ginkgo leaves (Japanese Patent Public Disclosure No. 2007-99660), a hop extract (Japanese Patent Public Disclosure No. 2002-58450) and so on are reported, but it is difficult to consider that these extracts have established safety because their starting materials are not usually ingested and people have little experience in eating them.
On the other hand, cyclic dipeptides including 2,5-diketopiperazine ring compounds are known to have various physiological activities, and it is expected that such dipeptides will grow in demand in the medical and pharmacological fields. Dipeptides can be designed to have additional physical properties and/or new functions, which cannot be seen in single amino acids, and hence they are expected to be applicable to a wider range than that of amino acids. Moreover, dipeptides are also known to have additional physical properties and/or new functions, depending on their structural differences, e.g., whether they are linear or cyclic.
As for cyclic dipeptides, reports as described below have been issued. For example, some reports have shown that pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(1-methylethyl)-,(3S,8aS) and pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(2-methylpropyl)-,(3S,8aS), which are generated in roasted cocoa (J. Agric. Food Chem. 2005, 53, 7222-7231) or in coffee (J. Agric. Food Chem. 2000, 48, 3528-3532), serve as bitter components, and that 21 types of cyclic dipeptides are generated from a heat-treated product of chicken meat (Eur. Food Res. Technol. (2004) 218:589-597). In addition, other reports have shown that 2,5-piperazinedione,3,6-bis(1H-indol-3-ylmethyl)-,(3S,6S) and pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(phenylmethyl)-,(3S,8aS) have an anticancer effect (J. Pharm Pharmacol. 2000 January; 52(1):75-82); pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(1H-indol-3-ylmethyl)-,(3S,8aS) and pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(phenylmethyl)-,(3S,8aS) have an antibacterial effect; and pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(1H-indol-3-ylmethyl)-,(3S,8aS) and 2,5-piperazinedione,3,6-bis(1H-indol-3-ylmethyl)-,(3S,6S) have an antifungal effect (Pharmazie 1999 October; 54(10):772-5). However, it has not been reported that cyclic dipeptides are useful for treatment and/or prevention of depression, or that cyclic dipeptides have an improving effect on learning motivation.